5a74bb2421fabc152c66acd5ee7b0141 pmc_10005220.pdf 4f13a990d84668b9100e2286bb263e6c69eb52d9 pmc_10005220.pdf 3aabcc215fa80e00fc4a711021260baa32bfd8236c6c109566c296ce7084294b pmc_10005220.pdf Title: Caffeine and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: Findings from Clinical and Experimental Studies Subject: The aim of this study was to assess the potential benefits of caffeine intake in protecting against the development of diabetic retinopathy (DR) in subjects with type 2 diabetes (T2D). Furthermore, we tested the effect of topical administration of caffeine on the early stages of DR in an experimental model of DR. In the cross-sectional study, a total of 144 subjects with DR and 147 individuals without DR were assessed. DR was assessed by an experienced ophthalmologist. A validated food frequency questionnaire (FFQ) was administered. In the experimental model, a total of 20 mice were included. One drop (5 L) of caffeine (5 mg/mL) (n = 10) or vehicle (5 L PBS, pH 7.4) (n = 10) was randomly administered directly onto the superior corneal surface twice daily for two weeks in each eye. Glial activation and retinal vascular permeability were assessed using standard methods. In the cross-sectional study in humans, the adjusted-multivariable model showed that a moderate and high (Q2 and Q4) caffeine intake had a protective effect of DR (odds ratio (95% confidence interval) = 0.35 (0.16–0.78); p = 0.011 and 0.35 (0.16–0.77); p = 0.010, respectively). In the experimental model, the administration of caffeine did not improve either reactive gliosis or retinal vascular permeability. Our results suggest a dose-dependent protective effect of caffeine in the development of DR, while the potential benefits of antioxidants in coffee and tea should also be considered. Further research is needed to establish the benefits and mechanisms of caffeinated beverages in the development of DR. Keywords: type 2 diabetes; diabetic retinopathy; caffeine intake; coffee consumption; tea consumption; retinal ganglion cell layer Author: Nuria Alcubierre, Minerva Granado-Casas, Patricia Bogdanov, Cristina Hernández, Hugo Ramos, Esmeralda Castelblanco, Jordi Real, Esther Rubinat-Arnaldo, Alicia Traveset, Marta Hernández, Carmen Jurjo, Jesús Vioque, Eva Maria Navarrete-Muñoz, Rafael Simó and Didac Mauricio Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Feb 27 12:14:50 2023 CET ModDate: Mon Feb 27 12:19:16 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1260406 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FLAGDG+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ACKGZT+VnURWPalladioL Type 1 Custom yes yes no 15 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 19 0 HHDURP+URWPalladioL-Bold Type 1 Custom yes yes no 23 0 HIBDBM+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 NIIKAV+URWPalladioL-Ital Type 1 Custom yes yes no 32 0 HGMNRX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 YFFKLH+CMSY10 Type 1 Builtin yes yes no 72 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 88 0 NBFCLH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 101 0 NBFCLI+PalatinoLinotype CID TrueType Identity-H yes yes yes 104 0 NBFCLJ+PalatinoLinotype TrueType WinAnsi yes yes no 110 0 NBFCLL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 113 0 OTQHUB+VnURWPalladioL-Italic Type 1 Custom yes yes no 127 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-21 02:36:00 CEST RepresentationInformation: pmc_10005220.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-07-20 02:27:28 CEST Size: 1260406 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 283 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Human Study Design and Subjects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Clinical and Socio-Demographic Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Caffeine Intake Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Experimental Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Assessment of Neurovascular Damage Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Clinical Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Experimental Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: Caffeine and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: Findings from Clinical and Experimental Studies Author: Nuria Alcubierre, Minerva Granado-Casas, Patricia Bogdanov, Cristina Hernández, Hugo Ramos, Esmeralda Castelblanco, Jordi Real, Esther Rubinat-Arnaldo, Alicia Traveset, Marta Hernández, Carmen Jurjo, Jesús Vioque, Eva Maria Navarrete-Muñoz, Rafael Simó and Didac Mauricio Subject: The aim of this study was to assess the potential benefits of caffeine intake in protecting against the development of diabetic retinopathy (DR) in subjects with type 2 diabetes (T2D). Furthermore, we tested the effect of topical administration of caffeine on the early stages of DR in an experimental model of DR. In the cross-sectional study, a total of 144 subjects with DR and 147 individuals without DR were assessed. DR was assessed by an experienced ophthalmologist. A validated food frequency questionnaire (FFQ) was administered. In the experimental model, a total of 20 mice were included. One drop (5 L) of caffeine (5 mg/mL) (n = 10) or vehicle (5 L PBS, pH 7.4) (n = 10) was randomly administered directly onto the superior corneal surface twice daily for two weeks in each eye. Glial activation and retinal vascular permeability were assessed using standard methods. In the cross-sectional study in humans, the adjusted-multivariable model showed that a moderate and high (Q2 and Q4) caffeine intake had a protective effect of DR (odds ratio (95% confidence interval) = 0.35 (0.16 0.78); p = 0.011 and 0.35 (0.16 0.77); p = 0.010, respectively). In the experimental model, the administration of caffeine did not improve either reactive gliosis or retinal vascular permeability. Our results suggest a dose-dependent protective effect of caffeine in the development of DR, while the potential benefits of antioxidants in coffee and tea should also be considered. Further research is needed to establish the benefits and mechanisms of caffeinated beverages in the development of DR. 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